Due to the difficulties in plugging high-pressure injection wells, the short period of plugging, and the use of modified nano-silica, a novel chemical gel plugging agent has been created. Modification of silica using silane coupling agents, and using the aqueous free radical polymerization method synthesized chemical plugging agent with AM, AA, and DMDAAC. The optimum synthesis conditions were screened by single-factor analysis: mass ratio m(AM):m (AA):m(DMDAAC) = 8:1.5:1, modified nano-silica concentration of 1.0%, total monomer mass concentration of 8.0%, initiator concentration of 0.3%, the cross-linker concentration of 0.4%, and coagulant concentration of 0.6%. The performance of the chemical plugging agent was evaluated under the target oil formation conditions. The experimental results showed that the chemical plugging agent exhibited good temperature resistance at 40-100 C, good salt resistance at mineralization (0.5-2.5) Â 10 4 mg/L, and the chemical plugging agent breaks through pressure gradients of 1.12, 15.42 and 90.15 MPa/m in the wellbore, fracture and core, respectively, compared with most gel plugging agents, this plugging agent is more suitable for sealing with pressure work. After adding the breakout agent, the fluid after breakout is fluid-like with low viscosity, which is convenient for reverse discharge and will not cause harm to the reservoir and ensure the subsequent normal construction operation.